Several studies have suggested that cardiac disease is a major cause of death in diabetes mellitus but the pathogenesis of the cardiac abnormality is not clear. Abnormalities of left ventricular function and composition have been observed in two animal models. It is planned to evaluate the relation of the level of hyperglycemia to these alterations and the influence on collagen and glycosaminoglycan accumulation in cardiac interstitium. Since normalization of glucose intolerance by treatment with insulin or tolbutamide in a canine model has not prevented the myocardial abnormalities, secondary hormonal responses may be operative. We propose to investigate the contribution of catecholamines and growth hormone to this process. Long-term studies planned in the Rhesus monkey will enable analysis of the relative evolution of coronary artery and myocaridal abnormalities, their correlation with degree of glucose intolerance and hyperlipoproteinemia and the influence of obesity. We will thus approach the question as to whether ventricular dysfunction or conduction abnormalities can progress without demonstrable cardiac ischemia.